Structural and kinetic studies of human aldh7a1 and aldh9a1

Abstract

The regulation and detoxification of endogenously and exogenously derived aldehydes is paramount to cellular survival due to the highly reactive nature of aldehydes as electrophiles. Human aldehyde dehydrogenases (ALDHs) are a superfamily of oxidoreductase enzymes that have critical roles in this regulation and detoxification. Misregulation of ALDH gene expression or mutations in the genes encoding for ALDHs lead to numerous disease pathologies. While extensive work has been conducted in understanding the metabolic roles and structures of these enzymes, there remains a need to further expand the structural and kinetic understanding of members of the human ALDH superfamily. This thesis aims to utilize the tools of structural biology and enzymology to expand the understanding of the ALDH superfamily.